Overcoming obstacles to metastasis - defenses against host defenses: Osteopontin (OPN) as a shield against attack by cytotoxic host cells

Osteopontin (OPN) serves both a cell attachment function and a cell signalling function via the α_vβ₃ integrin, in its cell attachment capacity it can promote attachment of both osteolasts to bone hydroxyapatite and various other cell types to basement membrane/extracellular matrix. In its cell signalling capacity it initiates a signal transduction cascade that includes changes in the intracellular calcium ion levels and the tyrosine phosophorylation status of several proteins including paxillin. Effects on gene expression include suppression of the induction of nitric oxide synthase by inflammatory mediators. OPN can also reduce cell oxidant and inhibit the killing of tumor cells by activated macrophages and endothelial cells. We hepothesize that those cancer cells that produce OPN at elevated levels can suppress the oxidative burst, inhibit NO production, and thus protect themselves from killing by specific host cell types.     

Reactive oxygen species (ROS) generated by cyanobacteria act as an electron acceptor in the biocathode of a bio-electrochemical system

The enhanced electricity generation in a biocathode bio-electrochemical system (BES) with Microcystis aeruginosa IPP as the cathodic microorganism under illumination is investigated. The results show that this cyanobacterium is able to act as a potential cathodic microorganism under illumination. In addition, M. aeruginosa IPP is found to produce reactive oxygen species (ROS) in its growth in the BES. ROS, as more competitive electron acceptors than oxygen, are utilized prior to oxygen. The BES current is substantially reduced when the ROS production is inhibited by mannitol, indicating that the ROS secreted by the cyanobacterium play an important role in the electricity generation of such a biocathode BES. This work demonstrates that the ROS released by cyanobacteria benefit for an enhanced electricity generation of BES.     

Antifungal activity of novel synthetic peptides by accumulation of reactive oxygen species (ROS) and disruption of cell wall against Candida albicans

In the present work, we investigated the antifungal activity of two de novo designed, antimicrobial peptides VS2 and VS3, incorporating unnatural amino acid α,β-dehydrophenylalanine (ΔPhe). We observed that the low-hemolytic peptides could irreversibly inhibit the growth of various Candida species and multidrug resistance strains at MIC₈₀ values ranging from 15.62 μM to 250 μM. Synergy experiments showed that MIC₈₀ of the peptides was drastically reduced in combination with an antifungal drug fluconazole. The dye PI uptake assay was used to demonstrate peptide induced cell membrane permeabilization. Intracellular localization of the FITC-labeled peptides in Candida albicans was studied by confocal microscopy and FACS. Killing kinetics, PI uptake assay, and the intracellular presence of FITC-peptides suggested that growth inhibition is not solely a consequence of increased membrane permeabilization. We showed that entry of the peptide in Candida cells resulted in accumulation of reactive oxygen species (ROS) leading to cell necrosis. Morphological alteration in Candida cells caused by the peptides was visualized by electron microscopy. We propose that de novo designed VS2 and VS3 peptides have multiple detrimental effects on target fungi, which ultimately result in cell wall disruption and killing. Therefore, these peptides represent a good template for further design and development as antifungal agents.     

Inhibition of nicotinamide phosphoribosyltransferase (NAMPT) activity by small molecule GMX1778 regulates reactive oxygen species (ROS)-mediated cytotoxicity in a p53- and nicotinic acid phosphoribosyltransferase1 (NAPRT1)-dependent manner

Cancer cells undergo mitosis more frequently than normal cells and thus have increased metabolic needs, which in turn lead to higher than normal reactive oxygen species (ROS) production. Higher ROS production increases cancer cell dependence on ROS scavenging systems to balance the increased ROS. Selectively modulating intracellular ROS in cancers by exploiting cancer dependence on ROS scavenging systems provides a useful therapeutic approach. Essential to developing these therapeutic strategies is to maintain physiologically low ROS levels in normal tissues while inducing ROS in cancer cells. GMX1778 is a specific inhibitor of nicotinamide phosphoribosyltransferase, a rate-limiting enzyme required for the regeneration of NAD(+) from nicotinamide. We show that GMX1778 increases intracellular ROS in cancer cells by elevating the superoxide level while decreasing the intracellular NAD(+) level. Notably, GMX1778 treatment does not induce ROS in normal cells. GMX1778-induced ROS can be diminished by adding nicotinic acid (NA) in a NA phosphoribosyltransferase 1 (NAPRT1)-dependent manner, but NAPRT1 is lost in a high frequency of glioblastomas, neuroblastomas, and sarcomas. In NAPRT1-deficient cancer cells, ROS induced by GMX1778 was not susceptible to treatment with NA. GMX1778-mediated ROS induction is p53-dependent, suggesting that the status of both p53 and NAPRT1 might affect tumor apoptosis, as determined by annexin-V staining. However, as determined by colony formation, GMX1778 long term cytotoxicity in cancer cells was only prevented by the addition of NA to NAPRT1-expressing cells. Exposure to GMX1778 may be a novel way of inducing ROS selectively in NAPRT1-negative tumors without inducing cytotoxic ROS in normal tissue.     

Assessing range re-expansion and recolonization of human-impacted landscapes by threatened species: a case study of the otter (Lutra lutra) in Italy

Detecting and understanding recoveries of threatened species from past and recent presence/absence data is essential to improving conservation efforts. However, false positive trends may be reported because of false absences in past data, therefore appropriate testing is needed. We tested an expansion/recolonization of the otter (Lutra lutra) populations in Italy from a fragmented distribution outlined in the 1984–1985 period by using Monte Carlo simulations. Land-use changes, human depopulation and decrease in influence of anthropogenic features were investigated as potential drivers of recolonization by using GIS modeling. A survey of the entire Italian range of the otter, conducted in 2002–2004, recorded a 2.2-fold increase in the proportion of occupied 10-km squares and 49 local colonizations. The range size and proportion of urban land-use in the 1984–1985 distribution were smaller (P < 0.05) than those derived from simulated surveys based on 49 random false absences versus colonization events. The distribution range expanded southward and nearly reached the southern margins of the peninsula. Recolonization of moderately urbanized landscapes was not accompanied by human depopulation. According to partial logistic regressions, the pure effect of urban land proportion and industry proximity on otter occurrence probability declined by about 48%, suggesting a decreased impact on the stream habitat. Conversely, natural factors, increased in importance by about 116%. The absence of a significant northward expansion in the 20 year period suggests that northward habitat restoration should be planned to encourage further recolonization. On the other hand, potential urban threats in the newly occupied landscapes should be controlled.     

Predicting savanna vegetation structure on the basis of plant available moisture (PAM) and plant available nutrients (PAN): a case study from Australia

The use of the plant available moisture (PAM)/plant available nutrients (PAN) concept to compare savanna structure was examined using data from twenty Australian sites. Above-ground biomass was regressed on various combinations of seventeen different estimates of PAM (plant available moisture) and two estimates of PAN (plant available nutrients). The ratios of actual transpirational loss from the subsoil to potential evapotranspiration (PET), and total annual rainfall to PET, were most highly correlated with total biomass. Grass biomass is poorly predicted by PAM on its own, and requires inclusion of woody leaf biomass in the regression. PAN had little effect on total biomass, although it is likely to be important for other, functional aspects of vegetation. The woody : grass ratio is best predicted by an index involving the ratio of subsoil : topsoil moisture. For biomass comparisons the use of a detailed water-balance model to estimate PAM is not warranted.     

Diversity of management practices required to ensure conservation of rare and locally threatened plant species in grasslands: a case study at a regional scale (Lorraine, France)

The Lorraine region, in northeast France, harbours 77 protected plantspecies whose main localities are in grasslands. About 80% of them are very rareor rare (less than 15 localities) in that territory and are threatened by changes inagriculture. These species occur in a large range of grassland habitats,reflecting variability of climatic, hydrological and edaphic parameters, butalso of agricultural practices. A more precise analysis of managementrequirements was carried out for seven of these species, Euphorbiapalustris, Aster amellus, Pulsatillaalba, Carex hordeistichos, Thalictrumminus ssp. majus, Botrychiummatricariifolium and Ophioglossum vulgatum, whichwere represented on a triangle whose corners correspond to grazing, cutting andno or very low exploitation. It confirmed the large diversity of managementpractices required to ensure conservation of rare and threatened grassland plantspecies, even at a local level. These appropriate conservation measures havetherefore to be carried out or, at least, monitored by specialized natureconservation organizations.     

Effect of a polycyclic aromatic hydrocarbon on the phytoremediation of zinc by two plant species (Brassica juncea and Festuca arundinacea)

The redevelopment of contaminated land is becoming increasingly necessary under sustainable- development legislation; however, many of the contaminated sites are "orphan" sites and therefore require a low-cost remediation technology. These sites often contain a cocktail of pollutants including organics and inorganics. Phytoremediation provides a possible solution, but there is little information available on the tolerance of plant species to multiple pollutants and their ability to remediate in mixed-contaminant soils. The effect of a polycyclic aromatic hydrocarbon (pyrene) in soil upon the remediation of zinc by Brassica juncea and Festuca arundinacea was investigated under normal climatic conditions in the United Kingdom. Zinc was effectively removed from mixed-contaminant soils in the presence of both species, in comparison to a control treatment. Both species accumulated zinc in plant tissues in the presence of pyrene, but the growth of B. juncea was significantly reduced when zinc and pyrene were supplied in combination. Zinc was predominantly associated with root tissues for F. arundinacea, whereas B. juncea contained higher concentrations in shoot tissues. F. arundinacea provides a possible species to be used for the phytoremediation of brownfield sites, but further research is required to determine a range of species that may be used and their applicability to different contaminants.     

Reactive oxygen species (ROS) and antioxidative enzyme status in <Emphasis Type="Italic">Solanum lycopersicum</Emphasis> on priming with fluorescent <Emphasis Type="Italic">Pseudomonas</Emphasis> spp. against <Emphasis Type="Italic">Fusarium oxysporum</Emphasis>

In plants, ROS signaling and increase in activities of antioxidants are among defense responses. The present study describes the oxidative stress profiling in model host plant tomato (Solanum lycopersicum L.), during an invasion of the wilt pathogen Fusarium oxysporum f. sp. lycopersici with or without seed priming with Pseudomonas isolates M80, M96 and T109. Tomato seeds were primed with known Pseudomonas isolates M80, M96 and T109 and the forty-day- old plants were challenged with spores of F. oxysporum under greenhouse conditions. Leaf samples were collected at 0, 24, 48 72 and 96 h post fungal challenge and analysed for systemic level of oxidative stress parameters including total phenolics, proline, hydrogen peroxide, lipid peroxidation and enzymatic antioxidants. Disease incidence in the plants under greenhouse conditions was also calculated. Results revealed that priming with Pseudomonas isolates resulted in reduced oxidative stress in the host, during pathogen invasion. M80-priming showed highest antioxidative protection to the host plants during F. oxysporum invasion. The observed reduction in hydrogen peroxide and lipid peroxidation in primed plants was in agreement with the increased activities of the corresponding antioxidant enzymes. Greenhouse results showed that the highest wilt disease symptoms were with M80-priming followed by M96 and T109. The present study gives substantial evidences on the oxidative stress mitigation in response to Pseudomonas-priming on the model tomato-Fusarium interaction system.     

The effect of prey morphology on the feeding behaviour and population growth of the predatory rotifer Asplanchna sieboldi: a case study using five species of Brachionus (Rotifera)

1. We investigated the numerical response, functional response and prey preference of Asplanchna sieboldi to five different prey brachionids. We also analysed the feeding behaviour of the predator in terms of encounters, attacks, capture and prey ingested per unit time. 2. The five prey species (Brachionus havanaensis, B. rubens, B. patulus, B. macracanthus and B. calyciflorus) differed in their body size and spine length. 3. The population growth rates of A. sieboldi ranged from 0.074 ± 0.03 to 0.431 ± 0.02 depending on prey type and density. There was a significant impact of the spine length rather than body size per se on the population growth rates of the predator. 4. The maximum number of prey consumed depended on both body size and spine length. In the functional response analyses, the plateau was reached at a prey density of 4–8 ind. mL^?1. 5. There was a significant impact of prey density on the prey preference of the predator.     

Small prey size offers immunity to predation: a case study on two species of <Emphasis Type=Italic>Asplanchna</Emphasis> and three brachionid prey (Rotifera)

We tested the hypothesis that small prey can coexist with large predators. For this we confronted two predators (smaller Asplanchna brightwellii: 900 μm and larger A. sieboldi: 1400 μm) with three prey rotifers (smaller: Anuraeopsis fissa (70 μm); larger: Brachionus calyciflorus (200 μm) and intermediate: B. patulus (120 μm)) using functional response, prey preference, population growth and life table demography. Regardless of prey type, A. sieboldi was able to consume more prey than A. brightwellii and it consumed higher number of B. patulus than of B. calyciflorus or A. fissa. Prey preference experiments showed that A. brightwellii had no preference for B. calyciflorus regardless of prey density, while A. sieboldi preferred B. calyciflorus and avoided A. fissa. Data on population growth showed that A. brightwellii was always numerically more abundant than A. sieboldi. Prey type had a significant effect on peak abundances of A. sieboldi but not of A. brightwellii. Life table demography data revealed a significantly lower lifespan in A. brightwellii fed B. calyciflorus, compared to B. patulus, but not when compared to A. fissa. A. sieboldi lifespan was not affected by prey type. Depending on prey type and predator species, generation time varied from 2 to 3 days. Both lowest (0.38 d⁻¹) and highest (0.98 d⁻¹) population growth rates were observed in A. sieboldi. We suggest that reduced reproductive output in Asplanchna was caused by either large (B. calyciflorus) or small (A. fissa) prey. At natural densities of Anuraeopsis, it is unlikely that Asplanchna reaches abundances high enough to exterminate this prey. By its extremely small size (combining low energetic profitability with low encounter rates with predators) A. fissa may coexist with Asplanchna in nature. Dedicated to H. J. Dumont for his 65th year. Guest editors: S. S. S. Sarma, R. D. Gulati, R. L. Wallace, S. Nandini, H. J. Dumont and R. Rico-Martínez Advances in Rotifer Research     

Analysis of the potential geographic range of the Pacific oyster <Emphasis Type="Italic">Crassostrea gigas</Emphasis> (Thunberg, 1793) based on surface seawater temperature satellite data and climate charts: the coast of South America as a study case

Ecological niche modeling based on surface seawater (SST) and atmospheric (AT) temperature records was used to predict the potential range of distribution of Crassostrea gigas, focusing on the South American coast as a study case. In its native range, the species maintains self-sustaining populations at thermal regimes with mean SST ranging from 14.0° to 28.9°C for the warmest month and from −1.9° to 19.8°C for the coldest month of the year. Settlement is also constrained to mean AT varying between 15° and 31°C for the warmest month and between −23° and 14°C for the coldest month of the year. Latitudinal limits for the species’ distribution in South America predicted by the analysis of AT regimes were Valdivia-Chiloe Island (39.8o–42.0°S, Chile) and Pisco (13.4°S, Peru) on the Pacific coast, and San Julian port (49.3°S) (Argentina) and Garopaba-Rio Grande (28.0°–32.0°S, Brazil) on the Atlantic coast. Geographical limits of distribution predicted by analysis of SST regimes were Chiloe Island (42.0°S, Chile) and Mancora (4.1°S, Peru) on the Pacific coast, and Puerto Deseado ria (47.7°S, Argentina) and Paranaguá (25.7°S, Brazil) on the Atlantic coast. Therefore, SST regimes would expand the potential range on the Pacific coast equatorward relative to AT.